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E U R O P E A N U R O L O G Y 6 5 ( 2 0 1 4 ) 6 1 0 – 6 1 9

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Prostate Cancer

Comparisons of the Perioperative, Functional, and Oncologic

Outcomes After Robot-Assisted Versus Pure Extraperitoneal

Laparoscopic Radical Prostatectomy

Guillaume Ploussard *, Alexandre de la Taille, Morgan Moulin, Dimitri Vordos,Andras Hoznek, Claude-Clement Abbou, Laurent Salomon

Department of Urology, Hospital Henri Mondor, 51 Avenue du Marechal de Lattre de Tassigny, 94010 Creteil, France

Article info

Article history:Accepted November 22, 2012Published online ahead ofprint on December 1, 2012

Keywords:

Prostate neoplasm

Laparoscopy

Prostatectomy

Robotic surgery

Continence

Potency

Recurrence

Abstract

Background: In spite of the increasing use of robot-assisted radical prostatectomy(RALP) worldwide, no level 1 evidence-based benefit favouring RALP versus purelaparoscopic approaches has been demonstrated in extraperitoneal laparoscopic proce-dures.Objective: To compare the operative, functional, and oncologic outcomes between purelaparoscopic radical prostatectomy (LRP) and RALP.Design, setting, and participants: From 2001 to 2011, 2386 extraperitoneal LRPs wereperformed consecutively in cases of localised prostate cancers.Intervention: A total of 1377 LRPs and 1009 RALPs were performed using an extraperi-toneal approach.Outcome measurements and statistical analysis: Patient demographics, surgical param-eters, pathologic features, and functional outcomes were collected into a prospectivedatabase and compared between LRP and RALP. Biochemical recurrence–free survivalwas tested using the Kaplan-Meier method. Mean follow-up was 39 and 15.4 mo in theLRP and RALP groups, respectively.Results and limitations: Shorter durations of operative time and of hospital stay werereported in the RALP group compared with the LRP group ( p < 0.001) even beyond the100 first cases. Mean blood loss was significantly lower in the RALP group ( p < 0.001).The overall rate and the severity of the complications did not differ between the twogroups. In pT2 disease, lower rates of positive margins were reported in the RALP group( p = 0.030; odds ratio [OR]: 0.396) in multivariable analyses. The surgical approach didnot affect the continence recovery. Robot assistance was independently predictive forpotency recovery ( p = 0.045; OR: 5.9). Survival analyses showed an equal oncologiccontrol between the two groups. Limitations were the lack of randomisation and theshort-term follow-up.Conclusions: Robotic assistance using an extraperitoneal approach offers better resultsthan pure laparoscopy in terms of operative time, blood loss, and hospital stay. Therobotic approach independently improves the potency recovery but not the continencerecovery. When strict indications of nerve-sparing techniques are respected, RALP givesbetter results than LRP in terms of surgical margins in pathologically organ-confineddisease. Longer follow-up is justified to reach conclusions on oncologic outcomes.

sociation of Urology. Published by Elsevier B.V. All rights reserved.
# 2012 European As
* Corresponding author. Tel. +33 1 49 81 25 53; Fax: +33 1 49 81 25 [email protected] (G. Ploussard).
E-mail address: g.plous
0302-2838/$ – see back matter # 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.http://dx.doi.org/10.1016/j.eururo.2012.11.049

http://dx.doi.org/10.1016/j.eururo.2012.11.049

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http://dx.doi.org/10.1016/j.eururo.2012.11.049

E U R O P E A N U R O L O G Y 6 5 ( 2 0 1 4 ) 6 1 0 – 6 1 9 611

1. Introduction

Radical prostatectomy (RP) is a standard treatment for

localised prostate cancer. The first laparoscopic radical

prostatectomy (LRP) was performed in 1991 and thought

not to be feasible because of the excessive operative time

[1,2]. However, in the following years, the development of

minimally invasive surgery was driven by work in Europe.

Some centres can now report considerable experience and

are able to standardise the technique. Experienced surgeons

have described the various advantages of laparoscopy [3,4].

And yet LRP remains a technically demanding procedure and

requires a learning curve [4,5]. These difficulties and the

emergence of robotic assistance that improves precision led

laparoscopic urologists to develop the technique of robot-

assisted radical prostatectomy (RALP) [6–8]. One of the

purposes of the robotic assistance was to reduce the learning

curve, even in laparoscopically naive surgeons, without

sacrificing the oncologic standards established by the open

approach [8,9].

Recent reviews and meta-analyses of the literature

recently highlighted the potential benefit of RALP regard-

ing the functional outcomes [10,11]. In a recent meta-

analysis, Tewari et al. also found that total perioperative

complication rates were higher for LRP than for RALP [12].

Authors highlighted that the lack of randomised controlled

trials were drawbacks in all published studies. The two

first controlled trials comparing LRP and RALP were

recently published using a transperitoneal approach

[13,14]. Authors reported better functional results in

terms of potency favouring RALP in both series and only

in terms of continence recovery in one series. However,

only a few patients were included, limiting the power of

analysis in comparing low events rates such as positive

margins, operative complications, and severe inconti-

nence. Most of these series reported short-term experience

with the transperitoneal (but not the extraperitoneal)

approach.

The aim of our study was to compare the perioperative

parameters and the functional and oncologic outcomes

between pure LRP and RALP using an extraperitoneal

approach and performed in a high-volume laparoscopy

reference centre.

2. Patients and methods

2.1. Patient selection

Between July 2001 and December 2011, 2386 consecutive men

underwent a LRP including 1377 pure LRPs and 1009 RALPs. Indications

of surgery were identical in the cases of pure LRP or RALP. We performed

the first LRP and the first RALP in our department in 2001, and we have

been performing RALP routinely since 2006. The respective rates of LRP

and RALP procedures for RP were 95.6% and 4.4% before 2006, 55.9% and

44.1% during the period 2007–2009, and have been 4.6% and 95.4% since

2010. Most of the LRPs were performed by three senior surgeons (L.S.,

C.C.A., A.D.L.T.), and the total number of RALPs by two senior surgeons

(C.C.A., A.D.L.T.) who had performed >100 LRPs before starting the RALP

learning curve. Mean follow-up in our cohort was 50.4 mo (1–138 mo).

Mean follow-up was 39 and 15.4 mo in the LRP and RALP groups,

respectively. The study was carried out in accordance with our local good

clinical practice rules.

2.2. Surgical procedure

The da Vinci system including three robot arms and a single console (first

generation) was used for all RALPs. We described the surgical technique

and the different steps of the surgery previously [15]. The bladder neck was

incised circumferentially with an attempt to spare the it except for high-

risk prostate cancers at risk of seminal vesicle invasion (assessed by

preoperative magnetic resonance imaging [MRI]). A standard

lymphadenectomy was performed prior to the completion of the

vesicourethral anastomosis in patients whose Gleason score was >6

and/or prostate-specific antigen (PSA) was >10 ng/ml. A running

vesicourethral anastomosis was then performed. At the beginning of

the experience, a 3-0 polyglactin suture on a 5/8 circle tapered needle was

used. For 2 yr we used a bidirectional barbed suture to perform the running

anastomosis. The anastomosis started with a posterior reconstruction of

the rhabdosphincter as described by Rocco. An anterior reconstruction was

performed suspending the anastomosis to the Santorini plexus.

Preoperatively, potent low- or intermediate-risk patients underwent

a nerve-sparing procedure. An intrafascial dissection as a nerve-sparing

procedure could be proposed to very low-risk patients who were potent

preoperatively. Very low-risk prostate cancer was defined by a clinical

T1c cancer with favourable factors including a PSA < 10 ng/ml, a

moderate extent of cancer on positive cores, few cores involved with

cancer, and favourable MRI findings (iT1 or small iT2 cancer). The

urethral catheter was usually removed on postoperative day 7 with no

cystogram.

2.3. Database and statistical analysis

Data were collected prospectively into a database by a clinical research

assistant (MM) including preoperative clinical and biologic character-

istics, surgical data, and postoperative parameters. Pathologic assess-

ments of RP specimens by a senior pathologist were recorded. After

fixation, the apex and base (3-mm-thick slices) were removed from each

specimen and examined by the cone method. The prostate body was

step-sectioned at 3-mm intervals perpendicular to the long axis (apical-

basal) of the gland. Positive surgical margins were defined by the

presence of tumour tissue on the inked surface of the specimen. All

patients prospectively completed self-administered questionnaires

concerning their quality of life (European Organisation for Research

and Treatment of Cancer QLQ-C30) and their voiding and sexual

disorders (International Index of Erectile Function [IIEF]-5), preopera-

tively and at 1, 3, 6, 12, and 24 mo after RP. Potency was defined as the

ability to achieve an erection sufficient for penetration (full erections

or diminished erections are routinely sufficient for intercourse) with or

without the use of a phosphodiesterase type 5 enzyme inhibitor

(excluding cases with intracavernous injection of prostaglandin E

or vacuum). Urinary continence was assessed by questionnaires and

defined as the absence of pads (strict urinary continence). Continence

and potency results were studied in the overall cohort regardless of the

continence and potency status before surgery. Phosphodiesterase type 5

enzyme inhibitors were systematically proposed at patient discretion.

The use of oral erectogenic medications was not statistically different

between LRP and RALP groups. Biochemical recurrence was defined as

any detectable serum PSA (>0.2 ng/ml). Perioperative complications

were noted and reported according to the updated Clavien classification

[16]. The qualitative data were tested using the chi-square or the

Fisher test as appropriate. The quantitative data were analysed by the

Mann-Whitney test. Multivariable analyses used a regression logistic

model. In these multivariable analyses, we have only included the

patients operated beyond the 100 first cases of each procedure and

Table 1 – Preoperative characteristics of the overall cohort andcomparisons between laparoscopic radical prostatectomy androbot-assisted radical prostatectomy subgroups

Overall cohortn = 2386

LRPn = 1377

RALPn = 1009

p value

Age, yr, mean (IQR) 62.7 (9.9) 62.7 62.7 1.00

BMI, kg/m2, mean (IQR) 26.5 (4.6) 26.6 26.5 0.648

PSA, ng/ml, mean (IQR) 9.6 (4.8) 9.8 9.2 0.123

No. of positive

cores, mean (IQR)

4.1 (3.0) 3.9 4.5 <0.001

Clinical stage, %

T1c 81.3 81.0 81.8

T2a–b 15.9 16.2 15.6

T2c–T3 2.7 2.8 2.6

>T1c 18.6 19.0 18.1 0.764

Biopsy GS, % <0.001

6 63.4 65.7 60.1

7 30.9 29.4 33.0

8–10 5.7 4.9 6.9

BMI = body mass index; GS = Gleason score; LRP = laparoscopic radical

prostatectomy; RALP = robot-assisted radical prostatectomy;

IQR = interquartile range.


operated on by the two surgeons performing both LRP and RALP (A.D.L.T.

and C.C.A.). Time-dependent variables were compared using the

Kaplan-Meier method and a log-rank test. A double-sided p value

<0.05 was considered statistically significant. All data were analysed

using SPSS v.13.0 software (IBM Corp., Armonk, NY, USA).

3. Results

3.1. Perioperative parameters

Table 1 shows the preoperative characteristics of the

patient’s cohort according to the surgical approach. The

two groups (LRP vs RALP) were comparable in terms of PSA,

body mass index, age, and clinical stage. High-grade

prostate cancers involving a greater number of cores were

more frequently reported in the RALP cohort ( p < 0.001).

Shorter durations of operative time (129 vs 175 min) and

of hospital stay (4.0 vs 5.7 d) were reported in the RALP

group compared with the LRP group ( p < 0.001) even

beyond the 100 first cases of each procedure (Table 2). Mean

blood loss was significantly lower in the RALP group (515 vs

800 ml; p < 0.001). However, bladder catheterisation was

longer in the RALP group (8.0 vs 7.2 d).

The overall rate and the severity (defined by the Clavien

classification) of complications did not differ between the

two groups (Table 2). Detailed complications in each group

are listed in Table 3.

3.2. Pathologic findings, surgical margins, and follow-up data

The results of pathologic findings are listed in Table 4.

Findings in RP specimens did not differ between the two

Table 2 – Comparisons of intraoperative and postoperative data, compassisted radical prostatectomy groups


LRPn = 137

Perioperative data

Operative time, min, mean (IQR) 155.8 (60.0) 175.5

Blood loss, ml, mean (IQR) 680.3 (695.0) 800.3

Bladder catheterization, d, mean (IQR) 7.5 (4.0) 7.2

Hospital stay, d, mean (IQR) 5.0 (3.0) 5.7

Transfusion rate, % 3.9 4.7

Lymph node excision, % 44.4 43.8

Nerve-sparing procedure, %

No 22.4 24.1

Unilateral 11.4 13.1

Bilateral 66.1 62.9

Complications

Clavien

0 95.7 96.0

1 0.7 0.6

2 3.3 3.1

3 0.0 0.0

4 0.2 0.2

5 0.0 0.0

Anastomosis leakage, % 6.5 9.7

Anastomosis stenosis, % 1.3 1.7

LRP = laparoscopic radical prostatectomy; RALP = robot-assisted radical prostatec

Comparisons were made among the overall cohort and after excluding patientsy After excluding the first 100 LRPs and the first 100 RALPs of each surgeon.

groups in terms of Gleason score and pTNM stage ( p = 0.488

and 0.788, respectively). Patients operated on by RALP have

smaller glands compared with their counterparts operated

on by LRP (47.5 vs 53.0 g; p < 0.001). Overall, in univariable

analysis, the rate of positive surgical margins was signifi-

cantly higher in the RALP group (31.3 vs 26.6%; p = 0.038),

especially in the case of pT3 cancer ( p = 0.030). Multivari-

able analysis is shown in Table 5.

Classical prognostic factors were significantly associated

with positive margins: PSA, pTNM stage, and Gleason score.

The prostate volume was inversely correlated with the risk

lications between the laparoscopic radical prostatectomy and robot-

7RALP

n = 1009p value Beyond the learning curvey

p value

128.9 <0.001 <0.001

515.4 <0.001 <0.001

8.0 <0.001 <0.001

4.0 <0.001 <0.001

2.9 0.084 0.235

45.4 0.488 0.441

20.3 0.002 0.249

9.2

70.5

95.3 0.756 0.797

0.7

3.6

0.0

0.2

0.1

2.3 <0.001 <0.001

0.7 0.081 0.036

tomy; IQR = interquartile range.

operated on during the 100 first cases of each procedure.

Table 3 – Detailed surgical and medical complications in the twolaparoscopic radical prostatectomy and robot-assisted radicalprostatectomy groups

LRPn = 1377

RALPn = 1009

Medical complications

Death – 1

Urinary infection 32 32

Fever 1 8

Phlebitis 2

Pulmonary embolus 1 2

Atelectasia 1

Pneumonia 6 4

Ill-being 5 3

Angor 1 1

Threat syndrome 3 1

Myocardial infarction 2 3

Renal insufficiency 2 3

Retina detachment 1 –

Overall, % 4.1 5.9

Surgical complications

Haemorrhage 6 4

Rectal injury 11 3

Epigastric injury 4 3

Wound complications

Haematoma 9 14

Abscess 3 9

Retzius collection 20 23

Lymphorrhea 1 2

Lymphocele 5 9

Haematuria 13 19

Anastomosis leakage 22 14

Ileus 2 4

Neurapraxia 1 1

Bowel injury 1

Overall, % 6.8 10.5

LRP = laparoscopic radical prostatectomy; RALP = robot-assisted radical

prostatectomy.


of positive margins ( p = 0.004). The rate of positive surgical

margins increased over time and was 1.9-fold higher in the

period 2010–2011 compared with the earlier period

( p = 0.045). Surgical experience continuously improved

the margin status even beyond the 100 first cases of each

procedure. The rate of surgical margins decreased by 2.6-

fold after 500 procedures ( p < 0.001).

In multivariable analysis, RALP was not associated with

an increased rate of positive margins. On the contrary, we

observed a trend toward lower rates of positive margins in

the RALP group compared with LRP, but differences did not

reach significance.

This difference was significant in the subgroup of pT2

cancers revealing RALP as the favourable factor indepen-

dently associated with better oncologic control of margins in

organ-confined disease ( p = 0.030; odds ratio [OR]: 0.396).

In pT3 cancers, the type of procedure (LRP vs RALP) did

not affect the rate of surgical margins in multivariable

analysis ( p = 0.619). Only the PSA level and surgical

experience were independent predictors of positive mar-

gins in pT3 cancers ( p < 0.001 and p < 0.001, respectively).

Survival curves stratified by the surgical approach were

not significantly different in the overall cohort and in pT2,

pT3a, or pT3b subgroups (log-rank tests in Table 4) showing

an equal short-term oncologic control. According to the

D’Amico preoperative risk groups (Fig. 1), biochemical

recurrence–free survival curves were not significantly

different between the two procedures in the low-risk

(log-rank test: p = 0.672), intermediate-risk ( p = 0.928), and

high-risk groups ( p = 0.413). The surgical volume had a

significant impact on the recurrence-free survival in the LRP

group with better oncologic outcomes after 300 procedures

compared with the 300 first LRP procedures ( p = 0.027;

Fig. 2). No difference was reported in the RALP group

( p = 0.132). Overall, 221 and 92 salvage treatments were

reported in the LRP (16.0%) and RALP (9.1%) groups,

respectively.

3.3. Continence

In univariable analysis, the rate of continence was

significantly in favour of RALP at each postoperative visit

((Fig. 3; p < 0.001). Results of continence recovery in the

overall cohort are shown in Figure 3. When considering only

patients operated on beyond the learning curve of each

surgeon, differences remained significant; after 6 and 12

mo, the rate of continence was 59% and 48.8% in the cases of

LRP as compared with 72% and 83.6% in the cases of RALP.

In the multivariable analysis shown in Table 6, the only

factor independently associated with a better continence

recovery was age ( p = 0.002) at each time point. Table 6

illustrates the multivariable analysis at the 12-mo visit.

Surgical experience, nerve-sparing surgery, and surgical

approach (LRP vs RALP) were not independent predictors

for short-term (at 1, 3, and 6 mo) or long-term (at 12 and

24 mo) continence recovery. Surgical treatment for persis-

tent incontinence was more frequent in the LRP group as

compared with the RALP group ( p < 0.001). Use of the

Macroplastique injection, adjustable continence therapy

balloon, suburethral sling, and artificial sphincter were

reported in 3, 10, 17, and 13 cases in the LRP group versus 0,

2, 5, and 0 cases in the RALP group.

3.4. Potency

In univariable analysis, the rate of potency was significantly

in favour of RALP at each postoperative visit. This difference

remained significant in a subgroup of patients undergoing a

bilateral nerve-sparing preservation (Fig. 4; p < 0.001).

After 6 and 12 mo, 20% and 31.6% of patients were potent

after LRP compared with 42% and 57.7% after RALP,

respectively.

In the multivariable analysis shown in Table 6, age

( p = 0.001), nerve-sparing surgery ( p = 0.033; OR: 3.9), and

RALP ( p = 0.045; OR: 5.9) were significant independent

predictors of potency recovery 12 mo after surgery. These

factors were also associated with potency at each medical

visit during follow-up. Surgical experience, the surgeon, and

the date of intervention were not associated with this

functional outcome.

The evolution of IIEF-5 over time is reported in Table 7.

Only scores from patients undergoing a bilateral nerve-

sparing surgery were reported. The scores at baseline were

comparable in the two groups. After surgery, scores were

Table 4 – Comparisons of pathological features and follow-up data between the two groups (LRP versus RALP). Comparisons have been madeamong the overall cohort and after excluding patients operated on during the 100 first cases of each procedure. Biochemical recurrence hasbeen tested using a log-rank test


LRPn = 1377

RALPn = 1009

p value Beyond the learning curve*

p value

Pathologic findings

Prostate weight, g, mean (IQR) 50.7 (24.0) 53.0 47.5 <0.001 <0.001

Specimen GS, %

6 28.0 27.0 29.2 0.488 0.997

7 61.4 62.2 60.4

8–10 10.6 10.8 10.4

Pathologic stage, %

pT0 0.7 0.5 0.8 0.788 0.208

pT2a 10.5 10.2 10.9

pT2b 2.0 2.5 1.4

pT2c 45.4 45.8 44.8

pT3a 31.1 30.3 32.2

pT3b–pT4 10.2 10.5 9.8

Positive surgical margins, %

Overall 28.6 26.6 31.3 0.038 0.013

pT2 17.9 16.8 19.6 0.513 0.391

pT3 43.7 41.1 47.4 0.030 0.048

Follow-up data

PSA failure, % <0.001

Overall 14.7 18.0 10.3 0.753y 0.820y

pT2 6.2 7.9 3.7 0.794y 0.502y

pT3 27.5 33.5 19.7 0.663y 0.979y

Follow-up, mo, mean (IQR) 29.1 (36.6) 39.0 15.4 <0.001 <0.001

GS = Gleason score; LRP = laparoscopic radical prostatectomy; PSA = prostate-specific antigen; RALP = robot-assisted laparoscopic prostatectomy;

IQR = interquartile range.* After excluding the first 100 LRPs and the first 100 RALPs of each surgeon.y Log-rank test.


higher in the RALP group as compared with those reported

in the LRP at each time point. In the overall cohort,

comparisons confirmed this significant difference at each

time point favouring RALP.

4. Discussion

The use of the robotic system reduces both the difficulty in

performing complex laparoscopic techniques and the

learning curve compared with the pure laparoscopic

procedure. As noted earlier, the practice of the pure LRP

requires a steep learning curve [17,18]. Experience can

improve pathologic and operative outcomes well beyond

the initial learning curve with a plateau at 200–250

procedures [19]. The learning curve for RALP was thor-

oughly studied, and surgical teams were able to accomplish

comparable operative times after 12 or 18 cases [20,21].

Some studies comparing pure LRP and RALP were also

published and show interesting postoperative results for

RALP [22–24]. It is interesting to notice that each of the

parameters—operative, pathologic, or functional—requires

a different learning curve that should be assessed separately

in LRP and RALP procedures. The operative time should not

be the single variable evaluated to define the learning curve

and the surgeon’s expertise. However, due to a lack of large

randomised controlled trials, differences in patient char-

acteristics or surgical experience might explain differences

in outcomes between the surgical approaches. The two first

controlled trials comparing LRP and RALP using a transper-

itoneal approach were recently published [13,14]. Authors

reported better functional results in terms of potency

favouring RALP in both series, and only in terms of

continence recovery in one series. However, few patients

were included, limiting the power of analysis in comparing

low events rates such as positive margins, operative

complications, and severe incontinence. Most of these

series reported the midterm experience of the transper-

itoneal (but not extraperitoneal) approach. Concerning the

extraperitoneal LRP, Rozet et al. showed equivalent opera-

tive, postoperative, and pathologic results when comparing

the extraperitoneal and the transperitoneal approach [24].

Stolzenburg and co-workers also reported interesting

results regarding extraperitoneal LRP in terms of operative

parameters and surgical margin rate [23]. The extraperito-

neal approach proved to be a safe and reproducible

procedure, with a fast recovery after surgery [25].

Our results were in line with those published by

‘‘transperitoneal’’ surgeons. RALP offered advantages con-

cerning the perioperative parameters in terms of hospital

stay, operative time, and blood loss, even beyond the 100

first cases of each surgeon. The overall rate and the severity

of complications did not differ between the two groups.

However, there was a trend towards lower rates of

anastomotic complications in favour of RALP even beyond

the 100 first cases of each procedure. Robotic assistance

offers technical parameters that may improve the anasto-

motic procedure: a magnified three-dimensional (3D)

visual field, a greater range of instrument motion, and a

minimisation of tremor. Advantages of RALP regarding

decreased adverse events and severity of complications

Table 5 – Predictive factors for positive surgical margins inmultivariable analysis: overall cohort and pT2 subgroup

Surgical margins p value OR 95% CI

Overall cohort

Age 0.497 – – –

PSA <0.001 – – –

Prostate volume 0.004 – – –

pT2 disease <0.001 0.478 0.37 0.62

GS

6 – Ref. 1 – –

7 <0.001 2.176 1.56 3.04

8–10 <0.001 3.665 2.29 5.86

Date of intervention

Before 2006 – Ref. 1 – –

2007–2009 0.169 1.355 0.88 2.09

2010–2011 0.045 1.887 1.02 3.51

Surgeon experience beyond the learning curve

100–300 – Ref. 1 – –

300–500 0.035 0.724 0.54 0.98

>500 <0.001 0.382 0.26 0.57

Nerve preservation 0.130 1.254 0.94 1.68

Surgeon 0.407 0.878 0.65 1.19

Procedure

Pure laparoscopy – Ref. 1 – –

Robot assisted 0.057 0.559 0.31 1.02

pT2 cancers

Age 0.283 – – –

PSA 0.063 – – –

Prostate volume <0.001 – – –

GS

6 – Ref. 1 – –

7 <0.001 2.722 1.85 4.01

8–10 0.657 1.340 0.37 4.88


Before 2006 – Ref. 1 – –

2007–2009 0.253 1.426 0.78 2.62

2010–2011 0.026 2.715 1.13 6.54


100–300 – Ref. 1 – –

300–500 0.121 0.709 0.46 1.10

>500 0.001 0.387 0.22 0.68


Surgeon 0.692 0.917 0.60 1.41

Procedure


Robot assisted 0.030 0.396 0.17 0.91

CI = confidence interval; GS = Gleason score; PSA = prostate-specific

antigen.

[(Fig._1)TD$FIG]

Fig. 1 – Biochemical recurrence–free survival (RFS) curves stratified by theprocedure (laparoscopic radical prostatectomy [LRP] vs robot-assistedradical prostatectomy [RALP]) according to the preoperative D’Amicorisk group: low risk (log-rank test: p = 0.672), intermediate risk( p = 0.928), and high risk ( p = 0.413).


were not found. No significant difference in rectal injuries

was detected. Nevertheless, RALP demonstrated a signifi-

cant improvement of perioperative parameters, shortening

the duration of hospitalisation.

Regarding the continence rate and the time to conti-

nence, RALP performed better than LRP in univariable

models as highlighted by the recent meta-analysis from

Ficarra et al. [11]. Nevertheless, the prevalence of urinary

incontinence after prostatectomy is highly influenced by

numerous parameters such as patient characteristics,

surgeon experience, or continence definitions (no pad vs

safety pad). Drawbacks of a systematic analysis must be

taken into consideration such as the impossibility of

controlling surgical skills and individual surgeon factors

[11]. The integration of all potential predictive factors for

continence recovery is mandatory before drawing major

conclusions. Thus, in line with the prospective trial

[(Fig._2)TD$FIG]

Fig. 2 – Biochemical recurrence–free survival (RFS) curves stratified by thesurgical volume of each surgeon (100–300, 300–500, >500 procedures)for the laparoscopic radical prostatectomy (LRP) and the robot-assistedradical prostatectomy (RALP) groups. Curves were significantly differentafter 300 procedures in the LRP group (log-rank test: p = 0.027) but not inthe RALP group ( p = 0.132).

[(Fig._3)TD$FIG]

Fig. 3 – Continence recovery rates at each medical visit in the laparoscopicradical prostatectomy and the robot-assisted prostatectomy groups(overall cohort). The p values at each time point were preoperative( p = 0.213), 1 mo ( p = 0.191), 3 mo ( p = 0.019), 6 mo ( p = 0.018), 12 mo( p = 0.177), and 24 mo ( p = 0.024).


published by Asimakopoulos et al., we did not find any

significant improvement of continence recovery in favour of

RALP after integrating all potential confounding factors in

multivariable analysis [14]. The impact of anterior or

posterior reconstruction on functional outcomes could

not be studied in our database. However, a recent review

did not find a benefit of such reconstructions on shortening

the time to continence recovery [26].

A recent meta-analysis based on four studies compar-

ing potency recovery after LRP and RALP only reported a

nonstatistical trend in favour of RALP [11,27,28]. The only

two prospective studies highlighted better functional

results in terms of potency favouring RALP. However, the

limited number of patients included did not allow

definitive conclusions. Comparisons are also subject to

debate because the incidence of potency recovery is

influenced by numerous factors. Our multivariable results

were in line with those published in the two level 2

studies [13,14]. The use of the robot was significantly

linked with a better recovery independently of surgical

experience, the surgeon, the date of the intervention, and

the practice of neurovascular preservation. After 6 and 12

mo, 20% and 31.6% of patients were potent after LRP

compared with 42% and 57.7% after RALP, respectively.

This difference remained significant after a 2-mo follow-

up. Our surgical technique is based on a retrograde

dissection using low-intensity bipolar cautery and clips.

We did not perform a strict athermal dissection that

might improve potency recovery [29]. However, the use of

a cautery-free technique has not definitively proved its

superiority and needs further evaluation. The fourth robot

arm potentially provides an adequate exposition avoiding

tractions of the bundles that may hinder potency outcomes.

We used a three-arm robot, and our experience with the four-

arm one is limited. However, the extraperitoneal approach is

surely not the best approach to use this fourth arm

extensively due to the limited space of the retroperitoneum.

Limitations of our report on functional outcomes were that

continence and potency require a short-term follow-up. Our

findings from the RALP cohort need to be confirmed. Another

drawback of the study is that our evaluation of the plane of

neurovascular bundle dissection is subjective and not based

on the pathologic outcome. Obtaining the intrafascial plane

may become more frequent and easier with the robotic

approach.

The first statistical analysis found higher positive

margin rates in the RALP cohort compared with those

reported in the LRP, especially in non–organ-confined

disease. Several factors with an impact on the risk of

margins might explain these differences. The RALP cohort

included patients at higher risk of positive margins. Those

patients had a significantly smaller volume of gland,

frequently showed an aggressive cancer on biopsy cores,

and were more often operated on using nerve-sparing

techniques. When all factors potentially linked with the

risk of margins were taken into account in a multivariable

Table 6 – Predictive factors for urinary continence and potency inmultivariable analysis: logistic regression model assessing thefactors predictive for continence and potency recovery 12 mo aftersurgery

p value OR 95% CI

Continence

Age 0.002 – – –

PSA 0.746 – – –


pT2 disease 0.393 0.782 0.44 1.37

GS

6 – Ref. 1 – –

7 0.751 0.915 0.53 1.60

8–10 0.699 1.239 0.42 3.68


Before 2006 – Ref. 1 – –

2007–2009 0.981 0.991 0.47 2.08

2010–2011 0.387 0.572 0.16 2.03


100–300 – Ref. 1 – –

300–500 0.230 0.678 0.36 1.28

>500 0.108 0.532 0.25 1.15


Surgeon 0.514 1.295 0.60 2.82

Procedure


Robot assisted 0.253 2.079 0.59 7.29

Potency

Age 0.001 – – –

PSA 0.085 – – –


pT2 disease 0.630 0.802 0.33 1.97

GS

6 – Ref. 1 – –

7 0.489 1.358 0.57 3.24

8–10 0.817 1.246 0.19 7.98


Before 2006 – Ref. 1 – –

2007–2009 0.976 1.021 0.25 4.10

2010–2011 0.467 0.497 0.08 3.27


100–300 – Ref. 1 – –

300–500 0.085 3.029 0.86 10.71

>500 0.903 0.913 0.21 3.89


Surgeon 0.308 0.556 0.18 1.72

Procedure


Robot assisted 0.045 5.933 1.04 33.82

CI = confidence interval; GS = Gleason score; OR = odds ratio;

PSA = prostate-specific antigen.

[(Fig._4)TD$FIG]

Fig. 4 – Potency recovery rates at each medical visit in the laparoscopicradical prostatectomy and in the robot-assisted prostatectomy groupsafter bilateral nerve-sparing surgery (overall cohort). The p values ateach time point were preoperative ( p = 0.716), 1 mo ( p < 0.001), 3 mo( p = 0.001), 6 mo ( p < 0.001), 12 mo ( p < 0.001) and 24 mo ( p < 0.001).

Table 7 – Evolution of International Index of Erectile Function-5 scoreprostatectomy and robot-assisted radical prostatectomy*

IIEF-5 scores Baseline Month 1 Mo

Bilateral preservation

LRP 17.6 3.3

RALP 17.7 5.2

p values 0.847 <0.001

Overall cohort

p values 0.800 <0.001 <

IIEF = International Index of Erectile Function; LRP = laparoscopic radical prostate* Overall cohort and subgroups of patients undergoing bilateral nerve-sparing su


model, the pT3 margin rates were not statistically different

for each surgical modality. We found lower positive

surgical margin rates in pT2 disease for RALP compared

with LRP in line with recent reviews [12,30]. Potential

factors explaining this significant difference could be the

traumatic manipulation of the gland during the neurovas-

cular dissection in LRP and the magnified 3D vision

improving the capsular preservation provided by robotic

assistance. However, urologists performing RALP tend to

expand indications of nerve preservation, exposing

patients selected on nonstringent criteria to an increased

risk of positive margins. Due to the widespread acceptance

of active surveillance in low-risk prostate cancers, we have

observed an important stage migration towards more

aggressive and larger prostate cancers (pT3 and/or Gleason

8–10) in our surgical cohort for the past 5 yr. However,

when strict indications of nerve-sparing techniques are

respected, RALP performs better than LRP in terms of

surgical margins in pathologically organ-confined disease

and does not increase the rate of positive margins in non–

organ-confined cancers.

Positive surgical margins and perioperative parameters

are early outcome measures of importance in comparing

surgical modalities. Our findings showed equivalent bio-

chemical recurrence rates for RALP and LRP. Surgeon

volume did not have an impact on the biochemical

s over time and their comparisons after laparoscopic radical

nth 3 Month 6 Month 12 Month 24

6.1 7.0 8.2 8.1

8.8 10.6 11.5 13.5

0.001 <0.001 <0.001 <0.001

0.001 <0.001 <0.001 <0.001

ctomy; RALP = robot-assisted radical prostatectomy.

rgery.


recurrence survival in our series. However, this lack of

difference based on surgeon volume might reflect a low

power effect and be related to the short follow-up.

Sooriakumaran et al. previously reported that lower

surgeon volume was associated with an increased risk of

recurrence after >5-yr follow-up [31]. Biochemical recur-

rences, metastases, and survival statistics require long-term

follow-up to assess [9]. Although we previously reported

the oncologic safety of extraperitoneal LRP, a longer follow-

up is warranted to confirm it in RALP [25]. We would also

like to emphasise that data were collected prospectively but

reviewed in a retrospective manner that introduced an

interpretation bias.

Our statistical analyses highlighted that several factors

must be taken into account when determining functional

outcomes after RP. Many published studies did not include

all these factors with impact, thus limiting the power of

their conclusions. Level of surgical experience, changes of

surgical details over time, cancer characteristics, patient

characteristics, or extension of nerve-sparing surgery could

play a part in differential outcomes and introduce

interpretation biases when comparing surgical techniques.

Systematic reviews and meta-analyses are also limited by

multiple designs, and methodological factors have to be

considered too. The strength of our series was that we chose

to control all these potential confounding factors in

multivariable analyses.

5. Conclusions

Robotic assistance using an extraperitoneal approach

confers better results than the pure laparoscopic procedure

in terms of operative time, blood loss, and hospital

stay. There was no independent impact on continence

by surgical approach. The robotic approach improves

potency recovery at short-term follow-up compared with

pure laparoscopy. Urologists performing RALP tend to

expand indications of nerve preservation exposing

patients selected on nonstringent criteria to an increased

risk of positive margins. However, when strict indications

of nerve-sparing techniques are respected, RALP does not

increase the rate of positive margins. This study did not

lead us to a definitive recommendation for the robot

assistance approach, but it does suggests improved

perioperative parameters and potency recovery without

compromising oncologic control.

Author contributions: Guillaume Ploussard had full access to all the data

in the study and takes responsibility for the integrity of the data and the

accuracy of the data analysis.

Study concept and design: Ploussard, de la Taille, Salomon.

Acquisition of data: Ploussard, de la Taille, Moulin, Salomon.

Analysis and interpretation of data: Ploussard, de la Taille, Salomon.

Drafting of the manuscript: Ploussard.

Critical revision of the manuscript for important intellectual content:

Ploussard, de la Taille, Moulin, Vordos, Hoznek, Abbou, Salomon.

Statistical analysis: Ploussard.

Obtaining funding: None.

Administrative, technical, or material support: None.

Supervision: de la Taille, Abbou, Salomon.

Other (specify): None.

Financial disclosures: Guillaume Ploussard certifies that all conflicts of

interest, including specific financial interests and relationships and

affiliations relevant to the subject matter or materials discussed in the

manuscript (eg, employment/affiliation, grants or funding, consultan-

cies, honoraria, stock ownership or options, expert testimony, royalties,

or patents filed, received, or pending), are the following: None.

Funding/Support and role of the sponsor: None.

References

[1] Schuessler WW, Schulam PG, Clayman RV, et al. Laparoscopic

radical prostatectomy: initial short-term experience. Urology

1997;50:854–7.

[2] Guillonneau B, Vallancien G. Laparoscopic radical prostatectomy:

the Montsouris experience. J Urol 2000;163:418–22.

[3] Rassweiler J, Schulze M, Teber D, et al. Laparoscopic radical pros-

tatectomy: functional and oncological outcomes. Curr Opin Urol

2004;14:75–82.

[4] Stolzenburg JU, Rabenalt R, Do M, et al. Endoscopic extraperitoneal

radical prostatectomy: oncological and functional results after 700

procedures. J Urol 2005;174:1271–5.

[5] Rassweiler J, Hruza M, Teber D, Su L-M. Laparoscopic and robotic

assisted radical prostatectomy—critical analysis of the results. Eur

Urol 2006;49:612–24.

[6] Salomon L, Levrel O, de la Taille A, et al. Radical prostatectomy by

the retropubic, perineal and laparoscopic approach: 12 years of

experience in one center. Eur Urol 2002;42:104–11.

[7] Guillonneau B, El-fettouh H, Baumert H, et al. Laparoscopic radical

prostatectomy: oncologic evaluation after 1000 cases at Montsouris

institute. J Urol 2003;169:1261.

[8] Rassweiler J, Schulze M, Teber D, et al. Laparoscopic radical pros-

tatectomy with the Heilbronn technique: oncologic results in the

first 500 patients. J Urol 2005;173:761–4.

[9] Novara G, Ficarra V, Mocellin S, et al. Systematic review and meta-

analysis of studies reporting oncologic outcome after robot-assisted

radical prostatectomy. Eur Urol 2012;62:382–404.

[10] Ficarra V, Novara G, Ahlering TE, et al. Systematic review and meta-

analysis of studies reporting potency rates after robot-assisted

radical prostatectomy. Eur Urol 2012;62:418–30.

[11] Ficarra V, Novara G, Rosen RC, et al. Systematic review and meta-

analysis of studies reporting urinary continence recovery after

robot-assisted radical prostatectomy. Eur Urol 2012;62:405–17.

[12] Tewari A, Sooriakumaran P, Bloch DA, Seshadri-Kreaden U, Hebert

AE, Wiklund P. Positive surgical margin and perioperative compli-

cation rates of primary surgical treatments for prostate cancer: a

systematic review and meta-analysis comparing retropubic, lapa-

roscopic, and robotic prostatectomy. Eur Urol 2012;62:1–15.

[13] Porpiglia F, Morra I, Lucci Chiarissi M, et al. Randomised controlled

trial comparing laparoscopic and robot-asisted radical prostatec-

tomy. Eur Urol 2013;63:606–14.

[14] Asimakopoulos AD, Pereira Fraga CT, et al. Randomized comparison

between laparoscopic and robot-assisted nerve-sparing radical

prostatectomy. J Sex Med 2011;8:1503–12.

[15] Ploussard G, Xylinas E, Salomon L, et al. Robot-assisted extraperi-

toneal laparoscopic radical prostatectomy: experience in a high-

volume laparoscopy reference centre. BJU Int 2010;105:1155–60.

[16] Dindo D, Demartines N, Clavien PA. Classification of surgical com-

plications: a new proposal with evaluation in a cohort of 6336

patients and results of a survey. Ann Surg 2004;240:205–13.


[17] Poulakis V, Dillenburg W, Moeckel M, et al. Laparoscopic radical

prostatectomy: prospective evaluation of the learning curve. Eur

Urol 2005;47:167–75.

[18] Bollens R, Sandhu S, Roumeguere T, et al. Laparoscopic radical

prostatectomy: the learning curve. Curr Opin Urol 2005;15:79–82.

[19] Secin FP, Savage C, Abbou C, et al. The learning curve for laparo-

scopic radical prostatectomy: an international multicenter study. J

Urol 2010;184:2291–6.

[20] Patel VR, Tully AS, Holmes R, et al. Robotic radical prostatectomy in

the community setting—the learning curve and beyond: initial 200

cases. J Urol 2005;174:269–72.

[21] Ahlering TE, Skarecky D, Lee D, et al. Successful transfer of

open surgical skills to a laparoscopic environment using a robotic

interface: initial experience with laparoscopic radical prostatec-

tomy. J Urol 2003;170:1738–41.

[22] Joseph JV, Vicente I, Madeb R, et al. Robot-assisted vs pure laparo-

scopic radical prostatectomy: are there any differences? BJU Int

2005;96:39–42.

[23] Stolzenburg JU, Rabenalt R, Do M, et al. Endoscopic extraperitoneal

radical prostatectomy: the University of Leipzig experience of 1,300

cases. World J Urol 2007;25:45–51.

[24] Rozet F, Jaffe J, Braud G, et al. A direct comparison of robotic assisted

versus pure laparoscopic radical prostatectomy: a single institution

experience. J Urol 2007;178:478–82.

[25] Paul A, Ploussard G, Nicolaiew N, et al. Oncologic outcome after

extraperitoneal laparoscopic radical prostatectomy: midterm

follow-up of 1115 procedures. Eur Urol 2010;57:267–73.

[26] Rocco B, Cozzi G, Spinelli MG, et al. Posterior musculofascial

reconstruction after radical prostatectomy: a systematic review

of the literature. Eur Urol 2012;62:779–90.

[27] Park JW, Won Lee H, Kim W, et al. Comparative assessment of a

single surgeon’s series of laparoscopic radical prostatectomy: con-

ventional versus robot-assisted. J Endourol 2011;25:597–602.

[28] Hakimi AA, Blitstein J, Feder M, et al. Direct comparison of surgical

and functional outcomes of robotic-assisted versus pure laparo-

scopic radical prostatectomy: single-surgeon experience. Urology

2009;73:119–23.

[29] Ahlering TE, Rodriguez E, Skarecky DW. Overcoming obstacles:

nerve-sparing issues in radical prostatectomy. J Endourol

2008;22:745–50.

[30] Coelho RF, Rocco B, Patel MB, et al. Retropubic, laparoscopic,

and robot-assisted radical prostatectomy: a critical review of out-

comes reported by high-volume centers. J Endourol 2010;24:

2003–15.

[31] Sooriakumaran P, Haendler L, Nyberg T, et al. Biochemical recur-

rence after robot-assisted radical prostatectomy in a European

single-centre cohort with a minimum follow-up time of 5 years.

Eur Urol 2012;62:768–74.

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